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UNTANGLING MOLECULAR ORIGINS OF COLORECTAL CARCINOMAS AND ASSIGNMENT OF MAJOR PATHWAYS BASED ON CIMP/MSI/BRAF/KRAS/TP53/APC PROFILES FROM ENDOSCOPIC TISSUE SAMPLING

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F26475821%3A_____%2F16%3AN0000029" target="_blank" >RIV/26475821:_____/16:N0000029 - isvavai.cz</a>

  • Result on the web

  • DOI - Digital Object Identifier

Alternative languages

  • Result language

    angličtina

  • Original language name

    UNTANGLING MOLECULAR ORIGINS OF COLORECTAL CARCINOMAS AND ASSIGNMENT OF MAJOR PATHWAYS BASED ON CIMP/MSI/BRAF/KRAS/TP53/APC PROFILES FROM ENDOSCOPIC TISSUE SAMPLING

  • Original language description

    Poster at UEGW2016: Recent advances in molecular profiling have resulted in definition of molecular types of colorectal cancer based on genetic and epigenetic aberrations. Resulting from separate developmental pathways the different types are associated with distinct prognostic features, which can be utilized in clinical practice. The aim of this study was to assign molecular subtypes based on CIN/CIMP/MSI molecular phenotypes in combination with mutation status of (proto)oncogenes KRAS and BRAF and tumor suppressors TP53 and APC in large adenomas and in early and late carcinomas for assessment of patients prognosis. A prospective 3-year study has resulted in the acquisition of samples (fresh biopsies or FFPE sections from EPE or EMR) from 138 carcinomas along with associated clinical parameters including localization, grade and histological type from adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed on endoscopic tissue specimens using methylation-specific multiplex ligation-dependent probe amplification technique (MS-MLPA) for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability (MSI) and high-sensitive CE melting assay for multiplex detection of somatic mutations in KRAS, BRAF, TP53 and APC genes. We have identified carcinomas belonging into 5 major molecular subtypes: (i) 3x serrated CIMP+/BRAF+/MSI-; (ii) 9x serrated CIMP+/BRAF+/MSI+; (iii) 2x familial CIMP+/MSI+/BRAF-, (iv) 38x Traditional CIMP-/KRAS+/APC+ and (v) 18x Traditional CIMP+/TP53+. The remaining 68 carcinomas were resulting from other combinations. The complex molecular profiling using combination of phenotypes with somatic mutations of oncogenes and tumor supressors allows for efficient stratification of carcinomas with subsequent assignment of prognosis.

  • Czech name

  • Czech description

Classification

  • Type

    O - Miscellaneous

  • CEP classification

    EB - Genetics and molecular biology

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/NT14383" target="_blank" >NT14383: Use of cfDNA as a new intention for minimally-invasive diagnosis and precise molecular classification of colorectal tumors.</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů